1. Field of the Invention
The present invention is a novel crystal form of 17β-hydroxy-7α-(5′-methyl-2′-furyl)-pregna-4,9(11)-dien-3-one-21-carboxylic acid, γ-lactone.
The present invention includes a process for the transformation of a 3-enol ether Δ3,5-steroid to the corresponding Δ4,6-3-ketal steroid (I-P).
The present invention includes a process for the transformation of a Δ4,6-3-keto steroid or ketal thereof (I), to the corresponding Δ4-3-ketosteroid-7α-carboxylic acid (VI).
The present invention also includes a novel processes and novel intermediates to produce the pharmaceutically useful compound eplerenone.
Further, the invention includes processes for transformation of 11α-hydroxy-17-lactone (CI) or 11α-hydroxy steroids (CIV) to the corresponding Δ9(11)-17-lactone (CII) or Δ9(11)-steroids (CV) using a N-fluoroalkylamine reagents (CVI).
2. Description of the Related Art
There is no reliable method to predict the existence of a crystal form of a pharmaceutical. Further, if a material is crystalline there is no reliable method to predict its physical properties. Therefore, patents to novel crystal forms are well known. For example, U.S. Pat. No. 3,565,924 discloses and claims 25-hydroxycocalciferol (25-HCC) which is a non-crysalline solid. Later a novel crystal form, 25-HCC hemihydrate was patented, see U.S. Pat. No. 3,833,622. U.S. Pat. No. 4,521,431 discloses crystal forms 1 and 2 of ranitidine hydrochloride. U.S. Pat. No. 4,504,657 claims “crystalline 7-[D-.alpha.-(p-hydroxyphenyl)acetamido]-3-methyl-3-cephem-4-carboxylic acid monohydrate. U.S. Pat. No. 6,452,007 B1 claims the “S” and “T” crystal forms of 1-[5-methanesulfonamidoindolyl-2-carbonyl]4-[3-(1-methylethylamino)-2-pyridinyl]piperazine. U.S. Pat. No. 6,444,813 B2 claims a novel crystal form of a known antibacterial agent, linezolid.
International Publications WO01/41535 and WO01/42272 disclose crystal forms of pharmaceutical agent eplerenone.